Dec. 20, 1955
NOTES
was warmed gradually t o the boiling point. Reaction began immediately, and the solution boiled for 10-15 minutes without application of heat externally. During this time the solution became deep red, and carbon dioxide was evolved. When spontaneous reaction subsided, the solution was refluxed for 2.5 hours longer. Most of the excess reagent was distilled at atmospheric pressure (1 hour), and the residue was distilled in vacuo. There was obtained 19.2 g. (49%) of viscous, yellow oil, b.p. 119-127' (3.5 mm.), which crystallized immediately. Recrystallization from dry ether afforded 16.1 g. (41%) of pale yellow crystals, m.p. 076-78'. Further recrystallization raised the m.p. t o 80-81 Anal. Calcd. for C,H,O,N: C, 67.07; H , 4.38; N, 8.69. Found: C,67.36; H,4.56; N,8.92. The mixed m.p. with a sample of acetylanthranil prepare: from anthranilic acid2 (reported' m.p. 80-81'), was 80-81 . The infrared spectra (chf.) of the two samples were identical, having characteristic peaks a t 5.69-5.72, 6.08 and 6.23 p . The odor of the pure compound was as described previously.l 2-Acetylaminobenzoic Acid (IIIa).-M aterial obtained in the preceding experiment was treated with water, and the product was recrystallized from ethyl acetate. There was obtained colorless crystals, m.p. 182-184" (reported2 m.p. 185'), which were soluble in sodium bicarbonate solution and which did not depress the m.p. of an authentic specimen of acetylanthranilic acid when admixed with it. The infrared spectra of the two samples in chloroform and Nujol were identical in each case; bands a t 3.1-3.2, 5.92, 6.04-6 10, 6.23 and 6.32 p (Sujol) were observed. 6,7-Dimethoxy-2-methyl-3,1,4-benzoxazine( R . 1. 947) (IIb).-A mixture of 30.2 g. (0.125 mole) of 2-nitro-4,5dimethoxyphenylacetic acid and 200 ml. of acetic anhydride was refluxed for 2 hours. An exothermic reaction resulting in a deep red color was observed during the first 10 minutes of this period. The excess reagent was evaporated a t 100'. The residue crystallized, and was triturated with ethyl acetate. There was o b F e d 14.4 g. (52%) of orange crystals, m.p. 183-185 . Recrystallization from ethyl acetate (Norit) gave yellow crystals, m.p. 185-186.5". The infrared spectrum (chf.) had intense peaks a t 5.74, 6.07 and 6.19 p . Anal. Calcd. for C11H1104N: C, 59.72; H, 5.01; N, 6.33. Found: C, 59.64; H , 4.97; N,6.32. 2-Acetylamino-4,5-dimethoxybenzoicAcid (IIIb) -A sample of I I b was warmed with water on a steam-one for 1.5 hours. Recrystallization from methanol-ethyl acetate (Norit) afforded colorless crystals, m.p. 223.5-224.5' dec. (reported'2 m.p. 228"). The infrared spectrum (Nujol) had a band a t 3.1-3.2 p and intense peaks a t 5.94, 6.09, 6.20 and 6.27 p . The compound was soluble in sodium bicarbonate solution. Anal. Calcd. for C11H130$N: C, 55.22; H , 5.48; N, 5.86. Found: C, 55.37; H , 5.55; N, 5.73. 2-Methyl-6,7-dimethoxy-4-quinazoIone(IVb) .-A sample (0.2 g.).of I I b was warmed with 20 ml. of concd. ammonium hydroxide solution on a steam-cone for a half-hour. Evaporation of the excess reagent and recrystallization of the residue from ethyl acetate gave slightly yellow crystals, m.p. 297-300' dec. The infrared spectrum (Nujol) had peaks a t 3.17 and 6.05-6.08 p. Anal. Calcd. for C11H1203N2:C, 59.99; H , 5.49; IY, 12.7. Found: C,60.05; H,5.64; N, 12.5. 2-Acetylaminobenzyl Alcohol.-A solution of 2.8 g. of IIa in 150 ml. of ethyl acetate containing 2 g. of 10% palladium-charcoal catalyst was shaken under hydrogen (40 lb.) at 80' for an hour. Filtration of the catalyst and evaporation of the solvent gave 2.8 g. of colorless crystals, m.p. 111-113'. Recrystallization from methanol raised the The comm.p. t o 114-115' (reported13 m.p. 115-116'). pound was very soluble in dilute mineral acids and moderately soluble in water. The infrared spectrum (chf.) had peaks a t 2.77,2.97 and 5.95-5.98 p . Anal. Calcd. for CgH1,OzN: C, 65.44; H, 6.71; N, 8.48. Found: C, 65.41; H,6.53; N, 5.37. Acetylation with acetic anhydride at 100" for 15 minutes gave the 0,N-diacetate of o-aminobenzyl alcohol, m .p.
91-93', after recrystallization from ether (lit." m.p. 91'). The infrared spectrum of this compound (chf.) had peaks a t 3.02,5.80 and 5.93-5.96 p . 4-Nitrophenylacetic Anhydride.-A mixture of 5 g. of 4nitrophenylacetic acid and 50 ml. of acetic anhydride was refluxed for 2 hours. Evaporation of the excess reagent and trituration of the residue with ether gave 3.5 g. of crystals, m.p. 131-137". Recrystallization from ethyl acetate (Norit) gave pale yellow crystals, m.p. 141-143", the infrared spectrum of which (chf.) had a characteristic twin peak, 5.48 and 5.70 p. Anal. Calcd. for CleH1207N2: C, 55.81; H , 3.51; N, 8.14. Found: C,55.93; H , 3.76; N, 7.92.
.
(12) J. L.Simonsen a n d M. G. Rau, J. Chem. Soc., 26 (1918) (13) K.Auwers, B c r . , 37, 2249 (1904).
6699
(14) H. G.Soderbaum and 0. Widman, ibid., 22, 1667 (1889).
LABORATORY OF CHEMISTRY OF NATURAL PRODUCTS NATIONAL HEARTINSTITUTE NATIOSALINSTITUTES OF HEALTH, PUBLICHEALTH SERVICE BETHESDA 14, MARYLAND
Hydrogenation of Purpurogallin and Its Derivatives BY GORDON N. WALKER AUGUST8, 1955 RECEIVED
Since the structure of purpurogallin (I) was established by Haworth and his collaborator^,^-^ few reports of further work with this interesting and easily-prepared benztropolone have appeared. A three-step reduction of tetramethylpurpurogallin to 2,3,4-trimethoxybenzsuber-6-onehas been rep ~ r t e d . This ~ method requires that purpurogallin be methylated completely at the outset, which process is unattractive from a practical point of view, since methylation of purpurogallin beyond the trimethyl ether stage is not achieved easily.la Catalytic hydrogenation of purpurogallin and its methyl ethers also has appeared unattractive because mixtures of products were obtained from such reactions in earlier workla when platinum catalysts were used. The use of 10% palladium-charcoal catalyst now has been found to give better results than were obtained previously in hydrogenation of compounds in this series. Purpurogallin is reduced to tetrahydropurpurogallin(I1) in 75% yield in the presence of this catalyst. That hydrogen enters the tropolone ring rather than the benzene ring in this reaction follows from the fact that I1 is converted by diazomethane in two stages to the trimethyl derivative 111, indicating that three phenolic groups are present in 11. Conclusive evidence for structures I1 and I11 was obtained from further experiments. Compound I11 is an acyloin and as such is susceptible to oxidation under mild conditions. Thus with bismuth oxide in acetic acid,6 I11 was converted to diketone IV,293identified as the 2,4dinitr~phenylhydrazone,~m.p. 179-181'. The carbonyl group of I11 can be reduced, and this was accomplished in two stages. Hydrogenation in ethyl acetate a t 80' in the presence of 10% pal(1) R. D.Haworth, B. P. Moore and P. L. Pauson, J. Chcm. Soc., (a) 1045 (1948); (b) 3271 (1949). (2) D.Caunt, W.D. Crow, R. D. Haworth and C. A. Vodoz, i b i d . , 1631 (1950). (3) D. Caunt, W.D. Crow and R . D. Haworth, ibid., 1313 (1951). (4) A. Critchiow, R. D. Haworth and P. L. Pauson, ibid., 1318 (1951). (5) A. Eschenmoser and H. H . Rennhard, Helv. Chim. Acta, SO, 290 (1953). (6) W.Rigby, J . Chcm. Soc., 793 (1951).
NOTES
6700
OH,/0 XI11
AcO
VOl. 77
0 SI1
OH./O
IX
ladium-charcoal gave the diol VI while reduction in acetic acid under the same conditions led to formation of the benzsuberanol VI. The diol V dehydrated smoothly in the presence of 50% sulfuric acid and gave ketone VI1 in good yield, no rearrangement or other side-reactions being observed in OH this transformation. Ketone VI1 has been con011 OH XI sidered as an intermediate in proposed syntheses of x compounds related to colchi~ine,5~~ and thus preparation of VI1 by the new method described here of spectra, solubilities and melting points. In the is of special interest. The preparation of VI1 from new trimethyl derivatives 111, V and VI, all three I by way of 11,111,and V can be carried out in 2OY0 methoxy groups of necessity are attached to the over-all yield with no inconvenience other than benzene ring, while the lone hydroxy group is attached to the seven-membered ring. Clearly that involved in securing diazomethane. I n contrast with earlier reported results, la it has then the hydroxy group must be located in the been found that methyl ethers of purpurogallin benzene ring in the different series of compounds also may be hydrogenated smoothly in the presence VIII, IX, X and XI. The fourth, and singularly of l o yo palladium-charcoal. From experiments of unreactive, hydroxy group has been assigned to the this kind some new information concerning tri- 4-position (cf. 17111) on the basis of other evidence.' methylpurpurogallin has been obtained, and the This assignment is reasonable inasmuch as the 4structure VI11 earlier a d ~ a n c e d l - for ~ this com- position is a priori the most highly hindered pound has been substantiated further. By varying locality in the benzene nucleus, and also because solvent and temperature, VI11 was reduced in a hydroxy group in this position can chelate three distinct stages. From reduction of VI11 in strongly with the carbonyl group and thus be preethyl acetate a t room temperature, trimethyltetra- vented from behaving normally. That this reasonhydropurpurogallin IX was gotten quantitatively. ing is correct is indicated by some additional findFormerly this compound was obtained mixed with ings. The infrared spectrum of VI11 exhibits other products.la When reduction of VI11 was car- virtually no hydroxy absorption near 3.0 p and ried out in the same solvent a t go", an additional no carbonyl band in the 6.0 to 6.1 region, but molecule of hydrogen was absorbed, as in the case of rather an intense doublet a t 6.25-6.32 p , in conreduction of I11 to V,and diol X was produced. trast with the spectrum of tetramethylpurpuroFinally, reduction of VI11 in acetic acid a t SO" gallin, which has a strong multiple conjugated resulted in complete hydrogenolysis of the car- carbonyl band a t 6.05-6.16 p . This effect must bonyl group and gave X I , a reaction analogous to be due to chelation which is well-known to result in I11 + VI. Compounds I X (1n.p. SS.5-SSo), X marked changes of this kind in hydroxy and car(m.p.. 129-131') and X I (rn.p. 91-93") were not bonyl group vibrations. More indicative is the identical with the similarly-constituted compounds fact that while the spectrum of non-chelated I11 I11 (m.p. 109-111"), V (n1.p. 17S-1SOo) and VI displays a strong carbonyl peak a t 5.95 p and a (m.p. 95.5-99.5"), as was evident from comparison hydroxy band a t 2.89 p, the spectrum of the similarly-constituted compound IX has neither of these (7) H. Rapoport and J. E. Campion, THIS J O U R N A L , 73, 2239 bands. Phenolic hydroxy absorption in the infra(1951).
Dec. 20, 1955
NOTES
red becomes strong, however, in X and XI when the carbonyl group is reduced. The same effect of chelation upon carbonyl vibration is observed also in acetyl derivatives; a strong carbonyl band (6.04-6.12 p ) appears only when all four hydroxy groups of purpurogallin are acetylated. Additional, and rather striking, evidence for the presence of an abnormal hydroxy group in compounds of this series was obtained from reduction experiments with acetyl derivatives. When tetraacetylpurpurogallin (XII)*v9was hydrogenated in the presence of 10% palladium-charcoal in ethyl acetate a t 80°, acetic acid was formed by hydrogenolysis of the hindered acetoxy group, and triacetyltetrahydropurpurogallin (XIII) was isolated. This compound was identical with material prepared by acetylation of tetrahydropurpurogallin with acetic anhydride. Structure XI11 for the triacetate was confirmed by the infrared spectrum, in which hydroxyl and conjugated carbonyl bands were absent, as in other 4-hydroxy compounds. Evidently the 4-hydroxy group resists reaction strongly in derivatives of tetrahydropurpurogallin as it does in those of purpurogallin itself, for compounds IX and XI11 cannot be methylated or acetylated further under ordinary conditions. However, i t is also apparent that the nature of the 6-substituent plays an important part in influencing the degree to which the 4-hydroxy group is hindered in the tetrahydro-series. Thus when a hydroxy group is present a t position 6, the 4hydroxy group can undergo transformations, as in I1 + 111, but when an acetoxy or methoxy group is attached a t position 6, as in IX and XIII, reactions a t position 4 are blocked completely.
2,3,4-Trimethoxybenzsuber-S-one-6-ol (ffI).-Methylation of tetrahydropurpurogallin was accomplished in two stages. A suspension of 8.8 g. of I1 in 300 ml. of methanol was treated with a dry solution of 5 g. of diazomethane (from 3 1 g. of N-methyl-N-nitroso-N'-nitroguanidine)in 900 ml. of ether. Brisk nitrogen evolution took place and the solid material dissolved. After the mixture had stood 4 days, crystals were deposited again. Most of the solvent was evaporated. The crystals were collected and were triturated with methanol. This first product (2.0 g.) was largely a monomethyl ether, and had m.p. 187-195 By repeated recrystallization (ethyl acetate) a pure sample of monomethyl ether, m.p. 202!-204°, was obtained. The methoxy group is assigned tentatively to the 3-position in this compound. Anal. Calcd. for Cl2Hl4Ofi: C , 60.50; H, 5.92; CHIO, 13.03. Found: C, 60.71; H , 6.09; CH20, 13.20. The monomethyl ether (6.0 g.) was dissolved in 300 ml. of methanol,. and the solution was treated with 7 g. of diazomethane in 1 1. of ether. Nitrogen evolution again occurred. After standing 5 days, the solution was evaporated and the residual oil was taken up in ether. The ether solution was washed with two portions of 5% sodium hydroxide solution and two portions of water, and was dried (magnesium sulfate). Evaporation of the solvent afforded oily crystals, trituration of which wit: cyclohexane gave 2.8 g. Recrystallization fro? (27%) of product, m.p. 105-109 cyclohexane gave colorless, dense crystals, m.p. 109-111 The infrared spectrum (chf) had peaks a t 2.89 and 5.95 p . The compound gave no color with ferric chloride. It reacted readily with acetic anhydride, and the resulting acetate (a glass) showed strong absorption a t 5.76 and 5.87 p in the infrared spectrum. Compound I11 also reacted very slowly with 2&dinitrophenylhydrazine, but the derivative could not be obtained in a satisfactory condition. Anal. Calcd. for Cl4H&: C, 63.14; H , 6.81; CHaO, 34.96. Found: C, 63.07; H , 7.07; CH30,34.99. Methylation of I1 with methyl sulfate in the presence of potassium hydroxide solution gave very poor yields of 111. 2,3,4-Trimethoxybenzsuber-5,6-dione (IV).-A solution of 0.2 g. of 111in 5 ml. of acetic acid was warmed on a steamcone and was treated with 1 g. of bismuth oxides in several portions (10 minutes). The cooled mixture was diluted with water and the product was extracted with ether. The organic solution was washed with water and was dried over magnesium sulfate. Evaporation of the solvent gave bright yellow, viscous oil (0.1 g.). The 2,4-dinitrophenylhydrazone was prepared in 65% yield from the crude ketone. Recrystallization from ethanol-ethyl acetate gave yellow-orange crystals, m.p. 179-181' (lit.s m.p. 180-181 "). 2,3,4-Trimethoxybenzsuber-5,6-diol(V) .-A solution of 1.0 g. of I11 in 200 ml. of ethyl acetate containing 1.0 g. of 10% palladium-charcoalla was shaken under hydrogen (40 lb.) a t 80" for 2 hours. Filtration of the catalyst and evaporation ;f the solvent gave 0.95 g. of crystalline diol, m.p. Recrystallization (ethyl acetate) raised the 172-177 Apparently this product consisted alm.p. to 178-181 most entirely of one isomer, probably the cis form. The infrared spectrum (Nujol) had peaks a t 2.96 and 3.10 p. Anal. Calcd. for C14HZ006: C, 62.67; H , 7.51; &so, 34.70. Found: C, 62.78; H,7.56; CHaO, 34.87. 2,3,4-Trimethoxybenzsuber-6-one(VII) .-A mixture of 0.80 g. of V and 20 ml. of 50% sulfuric acid was warmed on a steam-cone until the crystals dissolved and oil separated (half-hour). The cooled mixture was diluted with water, and the product was extracted with ether. The ether solution was washed with sodium bicarbonate solution and water and was dried (magnesium sulfate). Evaporation of the solvent gave 0.75 g. of yellowish oil, the infrared spectrum of which had an intense peak a t 5.89 p . The 2,4-dinitrophenylhydrazone was prepared in 95% yield from the crude ketone. Recrystallization from ethanol-ethyl acetate gave yellow crystals, m.p. 176.5-177.5' (lit. m.p. 177",6 m.p. 177-178"). Anal. Calcd. for C?OH?IOTNI: C, 55.81; H , 5.15. Found: C, 56.03; H , 5.33. ~2,3,4-Trðoxybenzsuberan-6-01 (VI).-Hydrogenation of 0.3 g. of I11 in 80 ml. of glacial acetic acid at 80" in the presence of 0.7 g. of 10% palladium-charcoalla for 1.8 hours gave, after filtration of the catalyst and evaporation of the solvent, colorless oil which crystallized slowly. Recrystallization from cyclohexane afforded colorless crystals, m.p.
Experimental"Jlll Tetrahydropurpurogallin (II).-A mixture of 10 g. of purpurogallin,12 5 g. of 10% palladium-charcoal catalyst,l3 200 ml. of ethyl acetate and 200 ml. of absolute ethanol was shaken under hydrogen (40 lb.) a t 80" for 3 hours. Two moles of hydrogen were absorbed, most of this amount being consumed in a half-hour. The mixture was filtered while still boiling hot,.and the catalyst was triturated with several portions of boiling ethanol. Crystalline product began to separate immediately as the filtrate cooled. The filtrate was evaporated to a small volume. The product was collected and was triturated with ethyl acetate. There was obtained 7.6 g. (75%) of yellow crystals, m.p. 222-226" dec. Recrystallization from ethyl acetate raised the m .p. to 230232" dec. (1it.I m.p. 232-233" dec.). The compound gave a deep red-green dichroic test with ferric chloride, and dissolved in 5y0 sodium hydroxide solution with formation of a greenish-yellow solution which discolored slowly in the presence of air. The infrared spectrum (Nujol mull) had distinct peaks a t 2.88 and 3.15 p (unbonded and bonded hydroxyl), and a multiple peak a t 6.14-6.28 p , in contrast with the spectrum of purpurogallin which displays bands at 2.95-3.08, 6.17 and 6.29 p , and which has an entirely different "fingerprint" pattern. Anal. Calcd. for CllHllO5: C, 58.92; H, 5.40. Found: C, 58.94; H , 5.32. Hydrogenation of I in acetic acid under the same conditions as described above gave I1 in 51% yield. (8) M. Nierenstein and C. W. Spiers, Bcr.. 46, 3151 (1913). (9) A. G. Perkin and F. M. Perkin, J. Chcm. Soc., 85, 243 (1904). (10) Melting points are corrected. (11) I am indebted t o Dr. William C. Alford and his staff for microanalytical d a t a and to Mrs. Iris Sewers and Mrs. H. F. Byers for infrared and ultraviolet spectra. (12) T. W. Evans and W. hl. Dehn, THISJOURNAL, 63,3647 (1930). (13) Obtained from Matheson, Coleman and Bell Co., Inc.
6701
.
.
.
".
.
6702
98.5-99.5'. The infrared spectrum (chf) had a rather weak band a t 2 -8-2.9 p . Anal. Calcd. for C14HzoOa: C, 66.64; H , 7.99. Found: C, 66.47; H, 8.05. Trimethylpurpurogallin (VIII) .-Purpurogallin (22 g.) was treated with a solution of 15 g. of diazomethane in 1500 ml. of ether. Nitrogen was evolved copiously. The mixture was allowed t o stand overnight, and the solvent was evaporated. Recrystallization of the residue from methanol afforded 18 g. (69%) of orange crystals, m.p. 172-177", raised t o 175.5-178' by further recrystallization (reportedla m.p. 176"). The infrared spectrum (chf) had a doublet a t 6.25-6.32 fi (shoulder a t 6.14 p ) and did not show any appreciable absorption in the region of 3.0 p . Tetramethylpurpurogal1in.-Complete methylation of purpurogallin and VI11 with methyl sulfate in the presence of 20% potassium hydroxide gave in each case the tetramethyl derivative, in low yield. Recrystallization of the neutral product from ether-cyclohexane afforded material, m.p. 92-93' (reportedla m.p. 94"). The infrared spectrum (chf) had a doublet a t 6.10-6.16 p ( shoulder a t 6.05 p ) . 2,3,6-Trimethoxy-4-hydroxybenzsuber-5-one(1x1.-Hydrogenation of 2.3 g. of VIII in ethyl acetate a t 25 in the presence of 1.0 g. of 5% (or 0.5 g. of 10%) palladiurn-charcoal for an hour in the usual way afforded 2.3 g. of product, m.p. 82.5-85 '. Recrystallization from cyclohexane or water gave pale yellow crystals, m.p. 86-88' (lit .la m.p. 86-87 "). The infrared spectrum (chf) had a peak a t 6.15-6.18 p , and did not display any absorption near 3.0 p . The compound was soluble in 573 sodium hydroxide solution and gave a deep purple ferric chloride test. The 2,4-dinitrophenylhydrazone was recrystallized from ethanol; yellow crystals, m.p. 156-158'. The reportedla m.p. of this derivative is 204". The reason for this large discrepancy is not clear a t present. Anal. Calcd. for C Z O H Z Z O ~C, N 53.81; ~: H , 4 97. Found: C, 53.54; H , 4.93. 2,3,6-Trimethoxy-4,5-dihydroxybenzsuberan (X).THydrogenation of 1.0 g. of VI11 in ethyl acetate a t 80" in the presence of 2 g. of 10% palladium-~harcoal~~ for 1.5 hours gave, after filtration of the catalyst and evaporation of the solvent, a mixture of glass and crystals. Trituration with ether afforded 0.4 g. of crystals, m.p. 119-123.5°. Recrystallization from cyclohexane gave colorless crystals, m.p. 129-131". The infrared spectrum (chf) had an intense peak a t 2.86 p . The compound gave a very weak green color with ferric chloride on standing. Anal. Calcd. for C14H&: C, 62.67; H , 7.51; Found: C, 62.87; H , 7.76. 2,3-Trimethoxy-4-hydroxybenzsuberan (XI j .-Hydrogenation of 2.7 g. of VI11 in 100 ml.of glacial acetic acid in the a t 80" for 2 presence of 1.8 g. of 10% palladi~m-charcoal~~ hours afforded viscous brown oil, after filtration of the catalyst and evaporation of the solvent. The crude material was dissolved in ether-ethyl acetate; the solution was washed with sodium bicarbonate solution and water, and was dried over magnesium sulfate. Evaporation of the solvents and distillation of the material in vacuo gave 1.4 g. of yellow, viscous oil, b.p. 150-165' (0.65 mm.), which material crystallized. Recrystallization from cyclohexaneethyl acetate afforded 1.2 g. of very pale yellow crystals, m.p. 91-93.5" (reported1am.p. 82"). The compound did not give a noticeable color with ferric chloride, but was readily soluble in 5 % sodium hydroxide solution. The infrared spectrum (chf) had a strong, sharp peak a t 2.8;i p . The mixed m.p. with compound VI was depressed (76-80'). Anal. -Calcd. for C14Hz~04:C, 66.64; H, 7.99. Found: C, 66.83; H , 7.97. Tetraacetylpurpurogallin (XII) .-Purpurogallin (4.2 g.) mas refluxed with acetic anhydride (50 ml.) for 2.5 hours. Evaporation of the excess reagent and trituration of the residue with ethyl acetate gave 4.4 g. of yellow crystals, m.p. 186-188", raised to 188-190 O after recrystallization from the same solvent (reportedQm.p. 184-186'). The infrared spectrum (chf) had a very intense peak a t 5.61-5.65 ~1 and a strong band at 6.04-6.13 M . Anal. Calcd. for C19Hp,09: C, 68.76; H, 4.15; Ac, 41.3. Found: C, 58.83; H , 4.17; Ac, 41.8. Acetylation of purpurogallin (1.7 8 . ) with a mixture of 30 ml. of acetic anhydride and 2 ml. of methanol (refluxei 1 hour) gave triacetylpurpurogallin (1.3 g.), m.p. 166-160 . '
VOl. 77
NOTES
Recrystallizatfi from ethyl acetate afforded orange crystals, m.p. 160-162 . The infrared spectrum (chf) had an intense peak a t 5.62-5.66 p and a weak band a t 6.08-6.11 p . Anal. Calcd. for CI,H&: C, 58.97; H , 4.08; Ac, 37.3. Found: C, 59.13; H , 4.48; Ac, 36.6. Triacetyltetrahydropurpurogallin (XIII).-A solution of 2.2 g. of XI1 in 200 ml. of ethyl acetate containing 2 g. of 10% palladium-~harcoal~~ was shaken under hydrogen (40 lb.) a t 80" for a half-hour. Filtration of the mixture and evaporation of the solvent gave glassy material which contained acetic acid. The material crystallized in the presence of methanol. Trituraiion with methanol gave 0.6 g. of product, m.p. 159-165 Recrystallization from t l y same solvent afforded colorless crystals, m.p. 169.5-171 The infrared spectrum (chf) had a triplet a t 5.60 (intense), 5.73 and.5.81 p , and did not show absorption in the 3.0 or 6.0 p regions. The compound did not give a ferric chloride test, but was soluble in 5% sodium hydroxide solution. Anal. Calcd. for C17H1808: C, 58.28; H, 5.18; Ac, 36.8. Found: C, 58.19; H, 5.22; Ac, 41.0. When the hydrogenation was allowed to proceed for longer periods a t 80 ", additional hydrogen was absorbed slowly, and no crystalline pi oducts were obtained. Acetylation of tetrahydropurpurogallin (11) in refluxing acetic anhydride for an hour gave colorless crystals, m.p. 170-171 ', after recrystallization from ethyl acetate. The mixed m.p. with material prepared as described above was not depressed, and the infrared spectra (chf and Nujol) were identical. Compound XI11 was recovered unchanged after treatment with bismuth oxide in warm acetic acid, and after attempted mcthylation n-ith diazomethane. L.4BORATORY O F CHEMISTRY O F NATURAL P R O D U C T S SATIOSAL HEARTISSTITUTE NATIONAL INSTITUTES O F HEALTH, PUBLIC HEALTH SERVICE BETHESD-4 14, M.4RYLAND
.
.
The Preparation of Some Alkyl Fumaric Acids and Maleic Anhydrides BY ~VY-YMAS R. VAUGHAN ASD KATHRYX S . ANDERSEN~ RECEIVED AUGUST11, 1955
Two general methods for the preparation of alkylfumaric acids and/or maleic anhydrides have been reported: one involves the conversion of paraconic esters to citraconic anhydrides by way of the itaconic acids,2 with subsequent conversion to the mesaconic acids by prolonged heating in aqueous alkali3 or by the action of bromine in carbon tetrachloride in the presence of ~ u n l i g h t . ~ Several unsuccessful attempts to prepare cyclohexylmaleic anhydride by this method5 led to the abandonment of this route, and though the alternative route was no more successful for this c o m p o ~ n d ,i ~ t proved to be very convenient for most of the desired substances. The new route, which involved dibromination of 2-alkylacetoacetic esters followed by alkali induced rearrangement to the alkylfumaric acids, was first reported by Demarcay6 in 1880, and was subsequently modified by Walden and other^.^,^ Table I lists the new 2alkylacetoacetic esters prepared for this purpose, (1) Abstracted from a portion of t h e Ph.D. Dissertation of Kathryn
G . Spackman, University of Michigan, 1954. ( 2 ) J. Houben, "Die ?Jethoden der Organischen Chemie," Vol. 111, G. Thieme, Leipzip. 1930, p. 8%. (3) G K . Almstrtirn, Bcr., 48, 2009 (1916). ( 4 ) K. Fittig and R . Glas-r, A i m , 304, 178 (1899). ( 5 ) K. G Spackmnn, Dissertation, University of Michigan, 195 I (appendix). (8) E. Demarcay, A n n c h i m . , 2 0 , 433 (1880). (7) P Walden, Ber., 24, 2025 (1891). (8) R. Anschiitz. Ann., 461, 155 (1928).
